SAN JUAN, P.R. – Stress can cause structural remodeling of the brain that can have short-term advantages, but if left unchecked, the changes can contribute to psychopathology, according to a presentation by a neuroendocrinologist at the annual meeting of the American College of Psychiatrists.
“The brain is capable of a lot of structural remodeling. The amygdala, hippocampus, and prefrontal cortex show remodeling that may be coordinated among these areas via neural connections,” said Bruce S. McEwen, Ph.D. Many mediators play a role, including insulin, glucose, and cytokines, neuroendocrinology studies show.
“Neuroscientists tended to think from the neck up, and endocrinologists tend to think from the neck down. So for a long time I was in between. But there is a growing appreciation of the mind-body connection [regarding stress],” said Dr. McEwen, Alfred E. Mirsky professor and head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, N.Y.
The downside of stress is well known. Dr. McEwen defined it as “the general process through which environmental demands result in outcomes deleterious to health.” Less appreciated are the positive aspects of stress, he said. For example, the stress response is how the body adapts in the face of a real or imagined threat to homeostasis. “Many people think of stress as a bad word with damaging effect on the body. The other side is stress is a challenge, and without our stress response hormones, we would not live long,” Dr. McEwen said. “A challenge can be invigorating as long as we can feel in command of the situation.” Dr. McEwen's insights come in part from his animal studies and in part from his work on humans in his neuroendocrinology lab.
Glucocorticoids such as cortisol can have beneficial and damaging effects, depending on the timing and duration of their release. For example, during acute stress, cortisol enhances immunity, memory, energy replenishment, and cardiovascular function, Dr. McEwen said. However, everything changes when chronic stress induces chronically high levels of cortisol. In this setting, cortisol suppresses immune function and memory, promotes bone mineral loss and muscle wasting, and increases long-term risks for metabolic syndrome and cardiovascular disease.
The body releases stress hormones in an attempt to return to homeostasis after an acutely stressful event. Chronic stress, however, can cause the body to maintain a different baseline state, called allostasis, Dr. McEwen said. Many elements–together called the “allostatic load”–can contribute to this altered state. Sleep deprivation, for example, is a common chronic stressor. People who are sleep deprived have increased blood pressure; elevated evening cortisol, glucose, and insulin levels; elevated inflammatory cytokine levels; increased appetite; depressed mood; and impaired cognitive function.
The adverse effects are many. “When you are 'stressed out,' you feel overwhelmed, out of control, exhausted, anxious, frustrated, or angry,” Dr. McEwen said. “Often you lose sleep, eat too much of the wrong things, drink excess alcohol, smoke, and neglect regular, moderate exercise.” The stress response spurs activation of many other mediators besides cortisol. Examples include the autonomic nervous system, prolactin, thyroid hormone, inflammatory cytokines, and other components of the neuroendocrine system and immune system.
“We have to recognize that the body works in this nonlinear fashion,” Dr. McEwen said.
He and his associates study “social neuroscience,” or how a person's social environment can have profound effects on brain function. Influences include daily stressors at home and work as well as major life events. “The brain's response determines not only the physiologic response to stress that leads to allostasis, but [also] the healthy behavioral responses, such as exercising, or detrimental responses, such as overeating or smoking, that can lead to allostatic overload.”
The hippocampus is a target for stress hormones. Structural changes are mostly seen in depression, he said. Patients with depression are more likely to have atrophy of the hippocampus and prefrontal cortex. Glucose, insulin, insulinlike growth factor 1, lipopolysaccharide, proinflammatory cytokines, and sex hormones are external factors that affect the hippocampus. “All of these may have an influence on mood and memory,” he said. “Recent evidence suggests [that the] hippocampus plays a bigger role than we thought in mood.”